Naturally-occurring molecule in tree leaves could treat anemia, other iron disorders
Boston Children's Hospital News May 19, 2017
ÂWithout iron, life itself wouldnÂt be feasible, says Barry Paw, MD, PhD. ÂIron transport is very important because of the role it plays in oxygen transport in blood, in key metabolic processes and in DNA replication.Â
New findings reported in the journal Science could impact a whole slew of iron disorders, ranging from iron–deficiency anemia to iron–overload liver disease. The team has discovered that a small molecule found naturally in Japanese cypress tree leaves, hinokitiol, can transport iron to overcome iron disorders in animals.
The multi–institutional research team is from the University of Illinois, Dana–Farber/Boston ChildrenÂs Cancer and Blood Disorders Center, Brigham and WomenÂs Hospital and Northeastern University. Paw, co–senior author on the new paper and a physician at Dana–Farber/Boston ChildrenÂs, and members of his lab demonstrated that hinokitiol can successfully reverse iron deficiency and iron overload in zebrafish disease models.
ÂAmazingly, we observed in zebrafish that hinokitiol can bind and transport iron inside or out of cell membranes to where it is needed most, says Paw.
This gives hinokitiol big therapeutic potential. ÂLike most things in life, too much or too little of a good thing is bad for you; the body seeks homeostasis and balance, says Paw.
Iron is needed so that the body can produce hemoglobin, a protein that carries oxygen in the blood of vertebrates. But if the bodyÂs iron–transporting proteins are absent, iron canÂt get where itÂs needed to help make hemoglobin: across cell membranes and inside the cells mitochondria.
ÂRed blood cells are the number one type of tissue in the body that need iron, so if iron–transporting proteins are missing, anemia can result, says Paw. ÂIron–deficiency anemia is the most common nutritional problem in the world.Â
On the flip side, itÂs not good if too much iron builds up inside cells. Iron overload can cause tissue damage, DNA damage and life–threatening organ dysfunction across the heart, liver and pancreas. This can be caused by a hereditary lack of iron–transporting proteins or from receiving frequent blood transfusions, which are often necessary during treatment for many different medical conditions.
A totally new approach to treating iron–transport disorders ÂIf youÂre sick because you have too much protein function, in many cases we can do something about it. But if youÂre sick because youÂre missing a protein that does an essential function, we struggle to do anything other than treat the symptoms, said the paperÂs co–senior author Martin Burke, MD, PhD, who led team members from University of Illinois. ÂItÂs a huge unmet medical need.Â
BurkeÂs team initially found that hinokitiol could transport iron across cell membranes in vitro. Then, they sought collaborators like Paw to test its efficacy in animal models.
In mammalian cell cultures, as well as zebrafish, mice and rats, Paw and collaborators saw that hinokitiol molecules can bind to iron atoms and move them across cell membranes and into/out of mitochondria, despite an absence of the native proteins that would usually carry out these functions.
ÂIf there is a genetic error, cell membranes wonÂt open for iron to come across, says Paw. ÂBut when you administer hinokitiol, it combines with iron and ferries it into, within or out of the cells and mitochondria where iron is needed. ItÂs a very interesting small molecule that has a lot of therapeutic potential!Â
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New findings reported in the journal Science could impact a whole slew of iron disorders, ranging from iron–deficiency anemia to iron–overload liver disease. The team has discovered that a small molecule found naturally in Japanese cypress tree leaves, hinokitiol, can transport iron to overcome iron disorders in animals.
The multi–institutional research team is from the University of Illinois, Dana–Farber/Boston ChildrenÂs Cancer and Blood Disorders Center, Brigham and WomenÂs Hospital and Northeastern University. Paw, co–senior author on the new paper and a physician at Dana–Farber/Boston ChildrenÂs, and members of his lab demonstrated that hinokitiol can successfully reverse iron deficiency and iron overload in zebrafish disease models.
ÂAmazingly, we observed in zebrafish that hinokitiol can bind and transport iron inside or out of cell membranes to where it is needed most, says Paw.
This gives hinokitiol big therapeutic potential. ÂLike most things in life, too much or too little of a good thing is bad for you; the body seeks homeostasis and balance, says Paw.
Iron is needed so that the body can produce hemoglobin, a protein that carries oxygen in the blood of vertebrates. But if the bodyÂs iron–transporting proteins are absent, iron canÂt get where itÂs needed to help make hemoglobin: across cell membranes and inside the cells mitochondria.
ÂRed blood cells are the number one type of tissue in the body that need iron, so if iron–transporting proteins are missing, anemia can result, says Paw. ÂIron–deficiency anemia is the most common nutritional problem in the world.Â
On the flip side, itÂs not good if too much iron builds up inside cells. Iron overload can cause tissue damage, DNA damage and life–threatening organ dysfunction across the heart, liver and pancreas. This can be caused by a hereditary lack of iron–transporting proteins or from receiving frequent blood transfusions, which are often necessary during treatment for many different medical conditions.
A totally new approach to treating iron–transport disorders ÂIf youÂre sick because you have too much protein function, in many cases we can do something about it. But if youÂre sick because youÂre missing a protein that does an essential function, we struggle to do anything other than treat the symptoms, said the paperÂs co–senior author Martin Burke, MD, PhD, who led team members from University of Illinois. ÂItÂs a huge unmet medical need.Â
BurkeÂs team initially found that hinokitiol could transport iron across cell membranes in vitro. Then, they sought collaborators like Paw to test its efficacy in animal models.
In mammalian cell cultures, as well as zebrafish, mice and rats, Paw and collaborators saw that hinokitiol molecules can bind to iron atoms and move them across cell membranes and into/out of mitochondria, despite an absence of the native proteins that would usually carry out these functions.
ÂIf there is a genetic error, cell membranes wonÂt open for iron to come across, says Paw. ÂBut when you administer hinokitiol, it combines with iron and ferries it into, within or out of the cells and mitochondria where iron is needed. ItÂs a very interesting small molecule that has a lot of therapeutic potential!Â
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